Candidate: I have faculty appointments in Nutrition and Dietetics at Saint Louis University and in Internal Medicine at Washington University. My education focused on exercise physiology and I have experience with clinical trials involving diet and exercise. My career goal is to perform independent research on the roles of exercise and nutrition in the prevention and management of diabetes and cardiovascular disease. The K01 Award will help me achieve this goal by providing support while I undergo the following training: I will learn how to perform frequently sampled oral glucose tolerance tests and "incretin effect" tests;I will learn how to conduct outpatient feedings as a dietary intervention;I will undergo training in data management, grant writing, grantsmanship, and responsible conduct in research;and, I will attend and present at scientific symposia and meetings. ENVIRONMENT: My affiliations with two universities will provide an excellent setting for my career development. At Saint Louis University I will grow as a dietetics researcher, as the environment is rich with dietetics experts and has the infrastructure that is necessary for conducting outpatient feedings. At Washington University, I have access to excellent facilities for performing metabolic tests and have strong working relationships with several experienced scientists who will provide their guidance and expertise. RESEARCH PLAN: I will conduct a randomized trail to assess the hypothesis that weight losses induced by caloric restriction (CR) and by exercise (EX) improve glucose tolerance and insulin action through partly distinct mechanisms and that the benefits from CR and EX are additive. To assess this hypothesis, glucoregulation will be assessed in 60 overweight, middle-aged men and women before and after 6% weight loss induced by 10-14 weeks of CR, EX, or CR+EX. Additional testing will be performed to explore candidate mechanisms for the improvements in glucoregulation. RELEVANCE The study findings may have implications for the prevention and management of hyperglycemia and insulin resistance, both of which are risk factors for type 2 diabetes. It is expected that greater health benefits can be obtained by using both caloric restriction and exercise than can be obtained from either treatment alone. Additionally, the findings may demonstrate that some of the benefits of caloric restriction are not attributable to weight loss, per se, and this may shed new light on the mechanisms involved in long-term blood sugar control.